Reactor systems

ABSTRACT

A reaction system comprising a reactor containing a reaction process medium and a heat exchanger providing a conduit through which flows a heat transfer fluid in which measurement of the flow and temperature change of the heat transfer fluid across the reaction is used to determine the heat generated or absorbed by the reaction system and that determination is used to monitor and control the reaction wherein  
     i. the average temperature difference between the heat transfer fluid and the processes fluid is from 1 to 1000° C. preferably 1 to 100° C.  
     ii. the temperature differential (t si −t so ) of the heat transfer fluid across the reaction system is at least 0.1° C., preferably at least 1° C.  
     iii. the linear velocity of the heat transfer fluid is at least 0.01 meters/second preferably 0.1 meters/second.

[0001] The present invention relates to reaction systems. Reactionsystems may involve physical and/or chemical changes. Chemical reactionsinvolve chemical change such as in the reaction of two or more moleculesto produce a new molecule including polymerisation, in the breakdown ofmolecules into two or more molecules. Physical reactions involve achange of state such as in crystallisation, precipitation, evaporation,melting, solidification and the like. Certain reactions can involve bothchemical and physical change.

[0002] The invention is concerned with improving the ability to monitorthe progress of physical and/or chemical reactions; it is also concernedwith improving the control of reaction systems through the improvedmonitoring. The improved control that is provided by the presentinvention enables the production of materials of higher quality andpurity, it enables more efficient use of reaction equipment and canfurther improve the efficiency of the equipment so that shorter reactiontimes are needed to obtain a given amount of material from a givenamount of starting materials. Another advantage is that smaller reactorsmay be used to produce a given volume of material. In addition theimproved control can lead to improved energy efficiency.

[0003] Many reactions are hazardous and care needs to be taken to ensureno accidents. The more accurate and more timely monitoring of thereaction provided by this invention enables reactions to be performedwithin stricter limits. This enhances safety and can reduce the reactioninefficiencies that, hitherto, were an inherent shortcoming of themanufacturing process. Furthermore, the ratios of reactants can beoptimised reducing the need for excess reactants to ensure completion ofa reaction.

[0004] Reactions whether they be physical, chemical or both generate orabsorb heat and there is therefore a heat change across the reaction.The theoretical heat generated or absorbed in a particular reaction isknown from established information. The actual heat generated orabsorbed during the course of a reaction could therefore, in theory, bea useful measure to determine reaction efficiency in the case of steadystate reactions and reaction progress in the case of batch reactions.

[0005] By way of an illustration of the theory, a typical chemicalsynthesis step will be considered. Two reagents (A and B) react togetherto form a new compound (C) as follows:

A+B C

[0006] where A=kmol of A

[0007] B=kmol of B

[0008] C=kmol of C

[0009] The heat generated by this reaction is established according tothe formula:

Q=Hr.C(kJ).

[0010] where Hr=heat of reaction per kmol of C produced (kJ/kmol)

[0011] C=kmol of component C produced (kmol)

[0012] The value of Hr may be determined from theoretical data orlaboratory calorimeters.

[0013] Currently the heat data described may be used in a variety ofways.

[0014] For any reaction, the maximum theoretical heat liberation can becalculated as follows:

Q′=Hr.C′(kJ)

[0015] where Q′=maximum theoretical heat generated (kJ)

[0016] Hr=heat of reaction per kmol of C produced (kJ/kmol)

[0017] C′=maximum theoretical yield of component C (kmol)

[0018] The maximum theoretical yield C′ is based on the assumption thatone or both of the feed components (A and B) are completely consumed.

[0019] If the heat of reaction is measured during a process, thequantity of component C synthesised at any time is as follows:

C=Q/Hr(kmol)

[0020] where C=quantity of C produced (kmol)

[0021] Q=heat measured during the reaction (kJ)

[0022] Hr=heat of reaction per kmol of C produced (kJ/kmol)

[0023] Thus the total mass of C can be calculated by knowing the totalheat absorbed or liberated and the heat of reaction (or crystallisationetc).

[0024] The expected theoretical yield of C is known from the quantity ofreactants present and the stochiometry of the process. Thus from theinformation above, the percentage conversion can be determined from theequation below. $\begin{matrix}{{where}\quad = {{C/C^{\prime}} \times 100}} \\{= {{percent}\quad {conversion}}} \\{C = {{quantity}\quad {of}\quad C\quad {produced}\quad ({kmol})}} \\{C^{\prime} = {{maximum}\quad {theoretical}\quad {yield}\quad {of}\quad {component}\quad C\quad ({kmol})}}\end{matrix}\quad$

[0025] In batch reactions, percent conversion ( ) provides an effectivemeans of identifying reaction end point and/or optimum reaction ratios.This can be used to reduce manufacturing time, improve plantutilisation, and reaction efficiency.

[0026] The present invention may also be used in laboratory activitiessuch as in laboratory calorimetry. Use of the techniques of the presentinvention can reduce or eliminate the errors in conventional jacketedcalorimetric measurement and simplifies temperature control duringcalorimetric measurement. In this way a quicker and more accurate methodfor the determination of theoretical Hr is provided. Unlike opticalanalytical devices, the calorimetric data is measured with inherentlysimple instruments which are not impaired by common process effects(fouling, composition change, temperature variation, mixed phases etc).Unlike optical analytical devices calibration of the calorimetricinstruments is not product specific and instruments can be tested andcalibrated on any fluid.

[0027] In continuous (plug) flow reactors, reaction efficiency ( )provides a parameter for controlling feed rate to the reactor andcontrolling process conditions. In this way it is possible to runconventional batch processes in small-scale plug flow reactors. Thisbenefits all aspects of the manufacturing process including lowercapital cost for equipment, increased plant versatility, improvedproduct yield, safer process conditions (through smaller inventories),greater product throughput and reduced product development time.

[0028] The ability to monitor reaction progress has an additional safetybenefit for both small and large reactors. A system with onlinecalorimetric data can instantly identify when unreacted compound isaccumulating in the reactor. This reduces the risk of runaways due toaccumulation of unreacted chemicals.

[0029] The design of reactors in common industrial use is howeverinherently unsuitable for measuring calorimetric data and thus thetechniques described remain theoretical.

[0030] Chemical reactors in common use in, for example, thepharmaceutical and fine chemical industries fall into four maincategories. Standard batch reactors in which reagents are mixed in astirred vessel in which heat is added or removed by means of heattransfer fluid recirculating though an external jacket. These are themost commonly used reactors for small-scale organic and inorganicsynthesis reactions. Batch reactors with internal coils, which are avariation on the standard batch reactor and have additional heattransfer surfaces within the body of the liquid. These reactors are usedfor general-purpose batch reactions where higher heat loads areencountered. Loop reactors in which reactants are pumped through anexternal heat exchanger and returned to the vessel. These are commonlyused for gas/liquid reactions in which case the liquid is returned tothe reactor via a spray nozzle to create a high gas/liquid interfacialarea. Continuous reactors in which reactants are pumped through a heatexchanger under steady state conditions. These are generally used forlarger scale manufacturing processes with long product runs.

[0031] The heat transfer characteristics of the four types of reactorsdescribed above have three common features:

[0032] i. The heat transfer fluid is circulated through the heatexchangers at high velocity to maintain favourable heat transfercoefficients. In the case of jacketed reactors, this is achieved byinjecting the heat transfer fluid into the jacket at high velocitiesusing nozzles or diverting flow around the jacket with baffles. In someinstances, coils for the flow of heat transfer fluid are welded to theoutside wall of the reactor vessel.

[0033] ii. High mass flow rates of heat transfer fluid are employed tomaintain a good average temperature difference between the heat transferfluid and the process fluid.

[0034] iii. The heat transfer area is fixed and temperature control ofthe process fluid is achieved by varying the temperature of the heattransfer fluid. In some cases limited scope exists for increasing ordecreasing the heat transfer area.

[0035] The features described above represent good design practice forachieving a flexible and optimised heat transfer capability within thereactor. However, these features do not lend themselves to measuring thequantity of heat generated or liberated. This deficiency is illustratedby reference to the chemical reaction between reagents A and B asdiscussed above. (It should be noted that the Example is not limited tochemical reactions and is equally applicable to other chemical andphysical processes).

[0036] When the two reagents (A and B) react together to form C, heat isliberated. The heat liberated per second can be expressed as follows:

q=Hr.c(kW)

[0037] where q=heat liberated per second (kW)

[0038] Hr=heat of reaction per kmol of C produced (kJ/kmol)

[0039] c=kmols of component C produced per sec (kmol/s)

[0040] If the process temperature remains constant the heat liberated(q) will be observed as a temperature rise in the heat transfer fluidaccording to the formula.

q=m.Cp(t _(si) −t _(so))(kW)

[0041] where q=heat absorbed by the heat transfer fluid which is theheat liberated by the reaction (kW)

[0042] m=mass flow rate of the heat transfer fluid (kg/s)

[0043] Cp=specific heat of heat transfer fluid (kJ.kg⁻¹K⁻¹)

[0044] t_(si)=temperature of heat transfer fluid in (° C.)

[0045] t_(so)=temperature of heat transfer fluid out (° C.)

[0046] However, in order to determine q, the flow rate and temperaturechange of the heat transfer fluid (t_(si)−t_(so)) must be measuredaccurately. In the reactor examples described above, effective designfavours high flow rates of heat transfer fluid. Often this leads to atemperature change of the heat transfer fluid (t_(si)−t_(so)) of lessthan 1° C. An IEC Class A RTD is one of the more accurate temperaturemeasurement devices available. These devices have a tolerance of ±0.25°C. (the error on the installed device may be higher).

[0047] Thus for a temperature change of 1° C., the accuracy of heatmeasurement can be expected to be ±25% or worse. This would rise to 250%where the heat transfer fluid temperature changed by 0.1° C. This factoralone makes it virtually impossible to measure the heat of reaction inconventional reactors. Furthermore, on a conventional reactor, heatleaking out of the system via the non-process side of the jacket cancreate serious error.

[0048] Furthermore, conventional chemical reactors often have sluggishcontrol systems which permit temperatures of the bulk material to cycleby a few degrees. In energy terms a few degrees change in temperaturecan represent a significant proportion of the overall energy release.

[0049] Conventional reactors offer acceptable heat transfercharacteristics when the flow of heat transfer fluid is held at a goodvelocity. Since the heat transfer surface is limited to 1 or 2 discreteelements, the range (of energy liberated or absorbed) over which auseful service temperature rise (t_(si)−t_(so)) can be achieved is verylimited. In a case where the energy release from the process is small,the temperature rise in the heat transfer fluid may be a fraction of adegree. In addition to this, the shaft energy of the heat transfer pumpcould be a high proportion of the total.

[0050] The limitations described above are common to all reactors (andevaporators, batch stills etc) used in the pharmaceutical, chemical andallied industries. Accordingly, when employing these reactors the heatgenerated or consumed by the reaction cannot be used to monitor theprogress of a reaction within any degree of accuracy.

[0051] It has been proposed in U.S. Pat. No. 6,106,785 that the heatgenerated in a polymerisation reaction may be used to monitor theprogress of the reaction. The system of U.S. Pat. No. 6,106,785 ishowever a coarse method for monitoring a reaction which involvesemploying an inferential sensor, whose concept is based on theobservation that for polymerisation processes, the amount of heatreleased is proportional, albeit in a non-linear way, to the degree ofthe monomer conversion. According to U.S. Pat. No. 6,106,785 by carefulcalculation of the reactor's thermal balance on-line one cancontinuously infer the degree of conversion and use it for control. Oncethe actual degree of conversion can be determined and ultimatelycontrolled, one can also control the cooling duty of the reactor andthus make it conform with the cooling capacity allotted to it by theplant scheduler. U.S. Pat. No. 6,106,785 is therefore concerned withoptimising the use of heat transfer fluid and the addition ofinitiator/inhibitor within safe operating parameters.

[0052] In U.S. Pat. No. 6,106,785 the batch controller data is useddirectly to control the reactor mixture temperature by manipulating theincoming coolant flow and temperature. The data are fed into theinferential sensor, where they are used to infer the current value ofthe degree of monomer conversion.

[0053] In U.S. Pat. No. 6,106,785 the degree of conversion is nottherefore measured directly, but it is inferred by dynamicallyevaluating the reactor heat balance. U.S. Pat. No. 6,106,785 thereforeenables one to infer the degree of conversion from the dynamicevaluation of the reactor heat balance. The use of the degree ofconversion replaces special sensors for feedback control with respect tothe product quality (end-use) properties. The use of the degree ofconversion also replaces physical time for the timing of process relatedoperations like valve opening and closing, and enables control of theheat supply/removal, dosing of the reactants, and so forth. The use ofthe sensor is said to allow an increase in the accuracy of theprediction of the batch evolution and thus enables a more accurateprediction of the cooling need profile than that provided by the systemspreviously used.

[0054] In U.S. Pat. No. 6,106,785, the reaction mixture temperature andthe integral heat rate are treated as two independent process variables.This approach is said to allow the user the freedom to specify batchrecipes in a way that defines the evolutions of either variable duringthe batch run, and to execute them under tight, high performancecontrol. Because the degree of monomer conversion is proportional to theintegral heat rate for many important polymers including PVC,controlling the two variables is said to allow the user independentcontrol over two basic determinants of products quality. According toU.S. Pat. No. 6,106,785 this control fully defines the heat release atevery instant of the batch run, thus making it possible to betterutilize the available cooling capacity through more reliable planningand scheduling. To control the temperature and integral heat rateindependently, the proposed method manipulates the amount of heat addedto or taken out of the reaction and the amounts of the initiator(s) andinhibitor added during the batch run.

[0055] Whilst these techniques bring benefits in optimising the use ofthe coolant they are not sufficiently accurate and discerning to enablesophisticated sensing and control of a reaction. The present inventionprovides the solution to this problem.

[0056] Accordingly, the present invention provides a reaction systemcomprising a reactor containing a reaction process medium and a heatexchanger providing a conduit through which flows a heat transfer fluidwherein measurement of the flow rate and temperature change of the heattransfer fluid across the reaction is used to determine the heatgenerated or absorbed by the reaction system and that determination isused to monitor and control the reaction wherein

[0057] i. the average temperature difference between the heat transferfluid and the processes fluid is from 1 to 1000° C., preferably from 1to 100° C.

[0058] ii. the temperature differential (t_(si)−t_(so)) of the heattransfer fluid across the reaction system is at least 0.1° C.,preferably at least 1° C.

[0059] iii. the linear velocity of the heat transfer fluid is at least0.01° C. meters/second, preferably at least 0.1 meters/second.

[0060] We have found that providing these criteria are satisfiedmeasurement of the flow rate and temperature change of the heat transferfluid across the reaction enables the heat generated or absorbed by thereaction system to be determined with a high degree of accuracy over awide range of operating conditions. The determination may then be usedto monitor and control the reaction with a high degree of accuracy.

[0061] Whilst any form of conduit may be used for the heat exchanger,pipes, plates or coils are preferred and the invention will hereafter bedescribed primarily in relation to a coil or coils.

[0062] In order for effective operation, the reaction system should havethe following characteristics:

[0063] a. The heat exchanger should have sufficient surface area toensure that a measurable temperature difference (t_(si)−t_(so)) isobserved in the heat transfer fluid as it passes across the reactor. Forthe purposes of accuracy, a temperature difference of more than 0.1° C.is preferred, more preferably more than 1° C. (preferably more than 5°C., most preferably more than 10° C.) is desirable.

[0064] b. A high temperature difference is preferably maintained betweenthe process fluid and the inlet heat transfer fluid (t_(si)) to ensurethat an accurately measurable service fluid temperature change(t_(si)−t_(so)) can be achieved and smaller heat transfer areas arerequired.

[0065] c. As far as possible, heat must only be transferred to or fromthe process fluid and not be transferred to other equipment or theenvironment to the extent

[0066] d. The heat transfer fluid must always flow at a reasonablevelocity. The velocity will vary with conduit, preferably coil, size andconditions but it is preferred that it is greater than 0.01meters/second preferably greater than 0.1 meters/second, most preferablygreater than 1 meters/second. Lower velocities will give slowertemperature control response. Low velocities also give a higher ratio ofthermal capacity (of the heat transfer fluid) to heat release rate. Thiswill compound errors in the values of measured heats.

[0067] e. When used for batch processes or multi-purpose duties, theheat transfer equipment should be capable of stable operation over awide range of energy release/absorbtion rates. The range will varyaccording to the nature of the reaction. In the case of batch reactionsa very wide operating range will be required.

[0068] To satisfy condition c above, the heat exchanger is preferablyimmersed in the process fluid and should be fully insulated at allpoints other than where fully immersed in the process fluid. Thisensures that all the heat gained or lost by the heat transfer fluid istransferred directly from and to the process fluid. This condition ismost easily achieved by designing the heat exchanger as a coil or platefully immersed in the process fluid.

[0069] It is further preferred that an optimal relationship between heattransfer surface area to heat transfer fluid flow capacity is provided.Such conditions exist when the heat transfer fluid (traveling at thedesired linear velocity) provides an easily measured temperature change(such as 10° C.) without incurring excessive pressure drop. It should benoted that the optimum heat transfer conditions vary according to theproperties of the process fluids and heat transfer fluids respectively.

[0070] In order to satisfy these criteria, the heat exchanger for thereactor is preferably a heat transfer coil, which preferably passesthrough the reaction fluid. The design of the coil is important toachieving the object of the invention and must be such that the heattransfer area matches the heat carrying capacity under specifiedconditions.

[0071] The techniques of the present invention may be used in systems inwhich the heat transfer fluid is straight through or recycled. We havefound however that the system of the present invention is most effectivewhen the heat transfer fluid is delivered at constant velocity andtemperature.

[0072] The heat transfer area of a coil may be related to the flowcarrying capacity of the liquid by using the formula

U.A.LMTD=m.Cp.(t _(si) −t _(so))(kW)

[0073] where U=overall heat transfer coefficient (kW.m⁻².K⁻¹)

[0074] A=heat transfer area (m²)

[0075] m=mass flow rate of heat transfer fluid (kg/s)

[0076] LMTD=log mean thermal difference between service and processfluids (° C.)

[0077] Cp=specific heat of heat transfer fluid (kJ.kg⁻¹K⁻¹)

[0078] (t_(si)−t_(so))=temperature (° C.) change in the heat transferfluid between inlet and outlet

[0079] The area A is the area that is in contact with the process fluid.

[0080] This information may then be used to optimize the heat transferfrom the heat transfer fluid to the heat transfer surface. This can beused to determine the optimum diameter to length relationship of anindividual coil whereby high turbulence is achieved without incurringexcessive pressure drop of heat transfer fluid through the heatexchanger (as shown by a high Reynolds number). Alternatively if theconduit is a plate the formula can be used to determine the optimumhydraulic path for the heat transfer fluid through the plate.

[0081] In order for effective operation it is preferred that

[0082] a. The temperature difference between the inlet heat transferfluid and the process fluid should be large enough (e.g. 5-100° C.) toensure that the heat transfer fluid undergoes a measurable temperaturechange (>1° C. or preferably greater than 10° C.) in its passage throughthe coil. The temperature change must not however be so high or low asto cause freezing, waxing out, boiling or burning of the process fluid.

[0083] b. The heat transfer area must be large enough to ensure that theheat transfer fluid undergoes a measurable temperature change(preferably >1° C. or more preferably greater than 10° C.) through theprocess fluid. Smaller temperature changes limit heat transfer capacityand accuracy. Higher temperature changes are desirable providing they donot cause freezing, waxing out, boiling or burning of the process fluid.

[0084] c. The linear velocity of the heat transfer fluid must bereasonably high (preferably >0.1 m.s⁻¹) in order to maintainsatisfactory control response and a good overall heat transfercoefficient.

[0085] d. The pressure drop of the heat transfer fluid flowing throughthe coil is from 0.001 to 20 or preferably 0.1 to 20 bar.

[0086] In practice, optimum coil lengths will vary according to thetemperature differences employed and the thermodynamic and physicalcharacteristics of the system. Calculating optimal coil length is aniterative process. A general-purpose device will be sized usingconservative data based on fluids with low thermal conductivity and alow temperature difference between the reaction fluid and the heattransfer fluid. Each coil will have a limited operating range. Smallvariation in coil length can be accomplished by varying the shape of thecoil such as by the provision of fins to increase surface area.

[0087] In a preferred system in which the heat transfer equipment iscapable of stable operation over a wide range of energy releases, thesystem is such that the area of heat transfer may be varied according tothe needs of the particular reaction (or stage of reaction). This may beconveniently accomplished by providing multiple heat transfer pipes,coils or plates each of which is designed to provide a certain degree ofheat transfer. In the case of pipes or coils, this may be achieved byestablishing the appropriate diameter and length relationship. In thepreferred multiple pipe system, the pipes may be brought into and out ofoperation as the needs of the reaction system dictates. Alternativelythe area of heat transfer may be varied by providing the reactor wall ora jacket for the reactor wall consisting of a series of conduits for theheat transfer fluid which can be brought into or out of operation as theneeds of the reaction system dictates. In this way the heat exchanger isor forms part of the vessel wall. Similarly the heat exchanger mayconsist of a series of plates which can be brought into or out ofoperation as the needs of the reaction system dictates. The use ofvariable area to improve temperature control provides faster and morestable temperature control and response and also enables a fixed userdefined heat flux.

[0088] Stable conditions in the open coils, particularly incalorimeters, give reduced interference due to temperature overshooteffects. Furthermore the control speed is faster in that the ability tomaintain the conduits at constant temperature permits a much highercorrecting temperature on a newly opened conduit. The control istherefore faster and more accurate.

[0089] Calorimetry refers to the measurement of heat entering or leavinga system. In the case of industrial processes, calorimetric data can bean extremely valuable guide to the health and progress of processoperations. The variable area design delivers calorimetric data which isincomparably better than conventional systems for the following reasons:

[0090] I. In conventional heat exchangers, large externally imposed heatfluctuations are used to control the process temperature. This ‘heatnoise’ combined with inherent control delay makes accurate calorimetryimpossible. When using the variable area design, the externally imposedfluctuations are virtually eliminated and the control delayssubstantially reduced.

[0091] II. Not only does variable area deliver better temperaturecontrol, it continues to do so whilst calorimetry is being measured.This reduces the problem of error and complexity associated withvariations in the system temperature.

[0092] III. The operating conditions can be set up to give aconsistently high temperature change in the heat transfer fluid, withoutcompromising temperature control performance. This enables accuratetemperature data to be collected.

[0093] The reaction system of the present invention is described withreference to the accompanying drawings in which FIG. 1 is a schematicillustration of a reaction vessel served with a single heat transfercoil (of specified diameter). FIG. 2 is a schematic illustration of acomparable reactor served with three heat transfer coils to providevariable heat transfer area.

[0094]FIG. 1 is a schematic illustration of a reactor (1) containing aprocess fluid (2) and a cooling coil (3) which is three meters long.This system is capable of accurately measuring energy changes of between72 and 260 watts. Measuring energy release rates of less than 72 wattsis achieved at the expense of lower accuracy (smaller temperature risein the heat transfer fluid) or slower control response (slower velocityof heat transfer fluid). Measuring energy release rates of greater than260 watts, introduces the risk of freezing (or burning/boiling whereheat was being applied) as very cold (or hot) heat transfer fluid has tobe supplied. The alternative of higher heat transfer fluid flow deliversonly moderate improvements (slightly improved U value and highertemperature difference between process and service fluids) in terms ofheat transfer capacity and is achieved at the expense of progressivelylower accuracy (smaller temperature rise in the heat transfer fluid).

[0095] The reactor in FIG. 2 has an improved measuring range of 72 to780 watts. The versatility has been increased by adding two more coils(4) and (5). When one coil is operating heat generation in the range of72 to 260 watts can be measured (as in the reactor of FIG. 1). With allthree coils operating (at a nominal maximum flow) up to 780 watts can bemeasured. By this method, it is possible to design a reactor with awider operating range.

[0096] In normal operation, the flow of heat transfer fluid to a coil(or set of coils) will be increased using a flow control valve. When anew coil switches in to accommodate a rising load, the control valvewill regulate the flow to ensure smooth transition to the higher flow.This will require a rapid flow control response to the step change inthe system pressure drop. To provide a smooth transition betweenoperating conditions and a wide operating range a large number of coilsare desirable. It should be noted that the performance of the heatexchanger is best served by having constant flow and temperature (of theheat transfer fluid) to the open conduits. Therefore, where flow controlis employed, it is better to limit this to the newly opening coils andto maintain constant flow and temperature to any other coils inoperation. Assuming sufficient conduits are employed, the alternativesolution is one on/off control (rather than flow control) for theleading coil. Alternatively the opening coil can fluctuate between theopen and closed position.

[0097] In terms of calorimetry stable conditions in the open coils givesreduced interference due to overshoot effects. In terms of control,maintaining coils at constant temperature permits a much highercorrecting temperature on a newly opened coil and this leads to reducedovershoot and is therefore faster and more accurate.

[0098] Instrumentation is a key aspect of successful operation of thesystems of the present invention. Accurate and sensitive instrumentationmust be used for measuring temperatures and the rate of flow of the heattransfer fluid. Instruments must operate over a wide range of flows andthis may be achieved by breaking up the coil system into separatemodules operated by manifolds. This enables different coils to bebrought into or out of operation according to the needs of the system.

[0099] Fast and accurate temperature measurements are a key performancerequirement. To achieve this, the temperature element is convenientlymounted in fast flowing heat transfer fluid. A minimum hold up volume(of service liquid) should exist between the temperature elements andthe heat transfer surface. This is achieved by using sub manifolds onthe discharge pipes as shown in FIG. 3.

[0100]FIG. 3 is a schematic illustration showing three differentialtemperature measuring devices (6), (7) and (8) on a seven-coil systembased on coils (9) to (15). These devices measure temperature change ofheat transfer fluid flowing across the coils. The temperature deviceswork in a cascade fashion. At low flow (coil 9 or coils 9 and 10operating) measuring device (6) is used for measuring dischargetemperature. When three or more coils are operating, measuring device(6) switches to idle and measuring device (7) takes over. When five ormore coils are operating, both (6) and (7) switch to idle and measuringdevice (8) takes over. This concept is applied irrespective of thenumber of coils and temperature devices used. It is preferred that thelinear velocity of the heat transfer fluid as it passes the temperatureelement is one meter per second or greater (although slower velocitiescan be tolerated). The temperature devices must be highly accurate andsensitive. It should be noted that separate inlet and outlet temperaturedevices could be used as an alternative to the differential devices.

[0101] In a preferred process, in addition to the normal processtemperature transmitters, which constantly measure the process acrossits entire range and provide the necessary safety interlocks, a secondpair of temperature elements can be provided to monitor the specificprocess set point. The arrangement uses two different types of measuringelements.

[0102] The main device is preferably an RTD, a 4 wire Pt100 RTD to{fraction (1/10)}^(th) DIN standard being especially suitable. Thetransmitter used to provide the 4-20 mA output signal is spanned to theminimum allowable for the transmitter (similarly any output signal typeor temperature span could be used). The temperature transmitter will becalibrated specifically at the process set point. Larger ranges willstill give acceptable results, but reducing the span to the minimumpossible offers improved accuracy and resolution. Thus this arrangementwill provide an extremely accurate means of process temperaturemeasurement.

[0103] The element of the temperature measurement system is the part ofthe device which is in contact with the liquid. In the case of an RTD,its resistance will change in response to changing temperature. Theresponse of an RTD is not linear. The transmitter is the calibrated partof a measuring device and is used to linearise the output to the controlsystem and convert the signal to an industry standard, usually 4-20 mA,but it could also be 1-5 V or 0-10V. A thermocouple's response to achange in temperature is a varying voltage. Usually milli volts per ° C.A thermocouple transmitter will again convert this signal to an industrystandard, again more often than not, 4-20 mA. Accordingly the term‘element’ is used when describing a physical mechanical presence in theprocess, e.g., a temperature element is located in the reactor andmeasures the temperature of the reactor contents. And the term‘transmitter’ is used when describing aspects of temperature measurementrelating to the control system, e.g., a temperature transmitter iscalibrated 0-100° C. and displays the contents temperature of thereactor.

[0104] The limitation of any RTD is its speed of response to a stepchange in temperature. Typically it can take up to four or five secondsfor an RTD to measure a change in temperature. Thermocouples, on theother hand, can respond much more rapidly to temperature fluctuations.For this reason a thermocouple is also used to monitor the process setpoint, a T type thermocouple being especially suited. Its transmitterwill be similarly ranged to the RTD. However, as a T type thermocouplehas an accuracy of only + or −1° C., it will not be used to monitor theprocess temperature. Its function is to monitor the rate of change ofthe process temperature.

[0105] The combined use of these two different types of sensing elementsprovides a temperature control system, which is both extremely accurateand responsive. It should be noted that not all process operationsrequire this level of temperature measurement accuracy and control. Insuch cases, more basic temperature control and measurement systems willprove tolerable.

[0106] In order to fully utilise this two-element approach, customsoftware is preferably used to determine which process variable(temperature, or rate of change of temperature) is the most significantat any one instance in time. Other temperature measuring devices such asoptical (e.g. Infra Red) may be used. Speed of measurement is importantfor effective operation of the system.

[0107] Accurate measurement of flow is also important for effectiveoperation. FIG. 4 shows a flow measurement system for the reactor shownin FIG. 3 employing multiple flow devices. Flow device (16) is a lowrange device for measuring flow when coils (9) or coils (9) and (10) arein operation. When three or more coils are in operation, flow device(17) takes over and (16) switches to idle. Any number of flowtransmitters can be used to achieve satisfactory accuracy. As a generalrule, the number of flow devices to be used should be calculated asfollows

Number of flow devices=(F _(max) −F _(min))/(R.F _(min))

[0108] where F_(max)=maximum flow (kg.s⁻¹)

[0109] F_(min)=minimum flow (kg.s⁻¹)

[0110] R=turn down ratio of the flow instrument

[0111] The above equation makes reference to mass flow. The equipmentcan use a volume flow device however provided the system converts volumeflow data into mass flow data. This can be done automatically by thecontrol software (mass flow=volume flow×liquid density). For sensitivesystems (or those with a wide temperature range) compensation should bemade for changes in liquid density. Information on liquid density can beinput manually into the control system. Alternatively, the controlsoftware can calculate the density based on temperature usingestablished mathematical relationships. Alternatively a mass flow devicemay be used.

[0112] In the present invention, the reactor is operated at constanttemperature. Any losses or gains in temperature to the environment willbe recorded as reaction activity. It is preferred that the system besuch that there is no direct heat transfer between the conduits. Wherethe conduits pass through the process fluid the process fluid itself mayprovide sufficient insulation to prevent direct heat transfer betweenthe conduits. If however the conduits are or form part of the vesselwall it may be necessary to provide insulation between the conduits.

[0113] In our preferred system three measures are used to take any heatlosses into account.

[0114] Heat losses are compensated for by zero calibration prior toreaction

[0115] The vessel is lagged or located in a box to minimise heat loss

[0116] For very sensitive systems the insulating box is temperaturecontrolled by an independent loop as shown in FIG. 5.

[0117] The arrangement in FIG. 5 shows a second heating cooling loopwith a fan (18) circulating air within the temperature-controlled box(19). The air temperature within the insulated box is determined bytemperature measurement device (20) and is maintained at the processreaction temperature (31). This eliminates heat loss/gain to/from theenvironment.

[0118] Any net heat flows in and out of the system must be monitored orcontrolled. Where liquids (or dry gases) enter or leave the system,these should be at reaction temperature. If not they should be of knownspecific heat and monitored for temperature and flow. Vapour carried outof the system presents a greater problem. If the gas flow issignificant, two options can be employed. Heat losses with off gas aremeasured in trial runs and compensated for in the calculations. Thissolution has to be used with care for batch operation when gas evolutionvaries with time. Accordingly for batch operation it is preferred thatthe gas flow out of the reactor be measured and the informationtranslated into heat flow data.

[0119] The system works most effectively under isothermal conditions. Itcan however be used for reactions where the process temperature changes.In this case it is necessary to measure the heat capacity of the systemas follows:

ΣM.Cp=(M _(p) .Cp _(p))+(M_(c) .Cp _(c))

[0120] where ΣM.Cp=heat capacity of the system (kJ/° C.)

[0121] M_(p).=mass of process fluid (kg)

[0122] Cp_(p)=specific heat of process fluid (kJ.kg⁻¹K⁻¹)

[0123] M_(c).=mass of equipment in contact with process fluid (kg)

[0124] Cp_(c)=specific heat of equipment in contact with process fluid(kJ.kg⁻¹K⁻¹)

[0125] In practice ΣM.Cp may be calculated by using the reactor. This isachieved by heating or cooling the process fluid and measuring heat lostor gained over a given temperature change when no heat is being absorbedor liberated by the process.

ΣM.Cp=Q/(t _(s) −t _(f))(kJ/° C.)

[0126] where ΣM.Cp=specific heat of the system (kW/° C.)

[0127] Q=measured quantity of heat added or removed (kJ)

[0128] t_(s)=temperature at the start of heating or cooling (° C.)

[0129] t_(f)=temperature at the finish of heating or cooling (° C.)

[0130] This heat capacity information may be fed into the system andused as a correction factor when the temperature changes during theprocess. The heat capacity information also serves as useful processdata.

[0131] Conventional reactors have fixed area heat transfer surfaces (oroccasionally several elements such as separate sections on the bottomdish and walls). They perform most effectively with a high and constantflow rate of heat transfer fluid to the jacket (or coils). Processtemperature is controlled by varying the heat transfer fluidtemperature. In the preferred system of the present invention, the areaof the heat transfer surface may be varied according to the needs of thereaction (although some variation in heat transfer fluid temperature canalso be used).

[0132] A typical control arrangement for control of the heat transferfluid using a variable area heat transfer surface is shown in FIG. 6. InFIG. 6 valves (21) and (22) are control valves that regulate flow ofheat transfer fluid to the heat transfer coils. The extent to which theyare open is determined by a temperature output measure from the reactor(or vessel). With the process at idle, valve (23) is open and sufficientflow permitted to compensate for heat gain from the agitator. As load isapplied to the process, valve (21) opens to permit the flow of more heattransfer fluid. When valve (21) is open beyond a pre-set point (or whenflow rate dictates) valve (24) will open and valve (21) will close upslightly to compensate. As valve (21) approaches the top of its controlrange, valve (22) takes over. As valve (22) progressively opens thevalves (23) to (29) are opened in a cascade fashion. In a preferredoperation greater constancy of the velocity of the heat transfer fluidwith the open coils is achieved by once a value is open it remains openand modulation of the flow is limited to the next coil to be broughtinto operation.

[0133] The required number of flow control valves can be calculated inthe same manner as for flow devices (see above).

[0134] Any number of control valves can be used and they can beinstalled in series (as shown) or in parallel. In this preferred systemthe extent to which valves 21 and 22 are open is dictated by the processload. The number of on/off valves (which turn the coils on and off) openis dictated either by the position of the control valves or the measuredflow.

[0135] The disadvantage with using flow control valves as describedabove is that they cause undesirable fluctuations in heat flow from anexternal source. A preferred alternative to this is a large supplymanifold held at constant pressure. This ensures that the open coilsalways see heat transfer fluid at constant flow and temperature. In thiscase, only the newly opening coils are subject to flow control (by flowregulations or on/off control). A further improvement of this controlsystem is the subject of United Kingdom Patent Application 0121375.0.

[0136] The heat transfer fluid is applied to the control equipment atconstant pressure and temperature. In some cases temperature can also bevaried where it is necessary to increase the operating range.

[0137] A key requirement of this invention is reliability. This isparticularly important in pharmaceutical applications where current goodmanufacturing practice (cGMP) dictates that the equipment operateswithin stated design parameters.

[0138] To provide a means of calibration and as a performance check, thereactor may be fitted with an electrical heater (or some other type ofreference heater). By supplying a measured current to the heater,reliable reference loads are provided for calibrating the system andchecking performance. In pharmaceutical applications, control and dataacquisition systems together with software should be validated to complywith cGMP standards.

[0139] The equipment may incorporate both conventional instrumentationand process specific instrumentation. These process specific instrumentsoperate at a higher than normal accuracy when compared to conventionalinstrumentation. FIG. 9 is a schematic illustration of typical processinstrumentation, which consists of:

[0140] A process temperature RTD instrument (31)

[0141] A process temperature thermocouple instrument (32)

[0142] heat transfer fluid differential temperature instruments (6), (7)and (8)

[0143] heat transfer fluid flow meter instruments (16) and (17)

[0144] For the process temperature RTD instrument (31) and the heattransfer fluid differential temperature instruments (6), (7) and (8),matching the RTD sensor to the temperature transmitter can result insignificant improvements. The specific characteristic of an RTD sensoris unique to each device. By storing this information in the transmitterimprovements in accuracy are obtained. The constants used in thistechnique are known as the Callendar-Van Dusen (CVD) constants. Thepresent invention is unique in that it uses additional calibration stepsto enhance the accuracy of its instrumentation. For example, if the CVDtechnique is coupled with the use of high accuracy RTDs (typically classB to {fraction (1/10)}^(th) DIN standard) process specific calibrationmay then be carried out to bring about further improvements in accuracy.

[0145] By ‘process specific calibration’, (e.g. the optimum reactiontemperature) we mean that the instrument is calibrated specifically atthe normal process set point of an instrument and that the measuringsystem error is adjusted, such that at this operating point bestaccuracy is achieved (for a normally calibrated instrument, bestaccuracy is usually given at the maximum calibrated range, or at a pointdictated by the characteristics of the sensor). For example if a processis to be controlled at 35° C., instrument (31) would be calibratedacross a small range, say 25 to 45° C. Furthermore, the instrumentswould be calibrated at 35° C. and adjusted so that at this specificpoint the error of the measuring system is the minimum achievable. Onceinstalled and connected to the control system, the calibration of theinstrument loop can be verified as a complete installation and anycontrol system errors compensated for. The control system hardware isdesigned to minimise errors (precision components must be used) and thusoptimise accuracy. Similarly the instrumentation installation must besuch as to minimise measuring error. The use of these additional steps,will allow maximum possible calibration accuracy to be obtained.

[0146] The process temperature thermocouple (32) may be calibrated in asimilar manner, but as it is used to measure rate of change oftemperature as opposed to temperature, its overall accuracy, althoughstill important, is less significant. Where high accuracy thermo couplesare available, they may be used as the primary measuring element.

[0147] The heat transfer fluid differential temperature measuringinstruments (6), (7) and (8) will also employ this same technique toensure best calibration accuracy is achieved.

[0148] For the heat transfer fluid flow instruments (16) and (17) thetechnique is again similar. Calibration in this instance is carried outover a small operating range with the emphasis on achieving the bestaccuracy at the preferred flow. By using multiple instruments calibratedover relatively small operating ranges, e.g. 0-1, 1-2, 2-3 etc., asignificant improvement in accuracy is achieved than by using a singleinstrument calibrated over the range 0-3. Best accuracy is achieved byusing a suitably sized instrument with a normal flow of 80 to 90% of theinstrument span. Again, once installed in the field and connected to thecontrol system, the calibration of the instrument loop should beverified as a complete installation and any control system errorscompensated for. The control system hardware is again designed tominimise errors and thus optimise accuracy.

[0149] Routine calibration of the heat measuring equipment may becarried out in several steps as follows:

[0150] The first step is zero calibration. For accurate operation, zerocalibration should be carried out for each type of process used. Thispermits the control system to compensate for any ‘non-process’ energychanges (e.g. heat gains and losses to the environment, energy gain fromthe agitator etc). The vessel is filled with liquid and the agitatorswitched on. It is then heated to the reaction temperature. When thetemperature is stable at the operating temperature, the heating/coolingsystem will function at a very low level to compensate for non-processenergy changes. The control system is zeroed under these conditions.

[0151] The second stage is to range and span the system. This is carriedout by heating or cooling with a reference heater/cooler. This may be inthe form of an electrical heater or an independent heating/cooling coil.Heating (or cooling) is carried out at several different energy inputlevels to range and span the system.

[0152] Alternatively the instruments may be tested individually in whichcase the second step of the above process may not be necessary.

[0153] We have found that the reactor systems of the present inventionare extremely useful as batch chemical synthesis reactors. We have alsofound that the invention enables the same size of machine to be employedfor development, pilot plant and full manufacturing purposes.

[0154] The preferred variable area heat transfer reactor is ideal forfast exothermic reactions, where it can operate as a small continuousflow reactor on processes hitherto conducted as batch reactions. Unlikelarge conventional batch reactors, it is possible to operate in thismode as the reaction is continuously monitored. Any fall off inconversion efficiency is detected immediately and forward flow isstopped. The arrangement for this system is shown in FIG. 7.Alternatively, the vessel shown in FIG. 7 might be a heat exchanger(without agitator) where turbulence is achieved by restricting thehydraulic path of the process fluid. The benefits of operating in thismode are various. The capital cost of a reactor for this type ofapplication is substantially lower than a conventional reactor. Inaddition higher throughputs can be achieved. This type of equipment isalso ideal for dangerous reactions as the inventory of reactants can bemuch smaller than that needed for conventional reactors. The equipmentcan also be programmed to stop reagent addition if unconsumed reactantstarts to accumulate.

[0155]FIG. 10 is a schematic exploded illustration of a plate heatexchanger which may be used in the present invention. FIG. 11 shows anexample of the flow of heat transfer fluid through the Plates (33),(34), (35) and (36) of plate heat exchanger of FIG. 10 and FIG. 12 showsa valve system which can be used to control the flow of the heattransfer fluid to the various plates which make up the plate heatexchanger.

[0156] A plate heater exchanger is generally made of several closelyassociated parallel plates and FIG. 10 shows four such plates (33),(34), (35), (36) exploded away from each other to show the fluid flowpaths available within the plates. According to the present inventionthe plates are provided with tubes (37) and (38) provided with openingswhich can be opened or closed to allow or prevent heat transfer fluidfrom entering a particular plate. A valve system (39), (40), (41), (42)and (43) is provided with plungers (42) and (43) so that the valvesystem can slide back and forth along holes (37) and (38) thus openingand/or closing the entrances to the individual plates. In this way thevalve system may be moved according to the determination of the heatgenerated or consumed by the reaction to provide temperature controlaccording to the present invention.

[0157]FIG. 12 is a cut-away cross-section of the assembled heatexchanger as illustrated in FIG. 10. FIG. 12 shows how the tubes (37)and (38) are provided with a series of openings (44) and (45) which,when open, allow the flow of heat transfer fluid into the plates. FIG.12 also illustrates how the openings may be opened and closed bymovement of the valve plungers (42) and (43) along the tubes.

[0158] A plate heat exchanger such as that shown in FIG. 10 may be usedin place of the coils in the systems shown in FIGS. 2 to 7.

[0159]FIG. 13 shows an alternative system in which the conduits (9),(10), (11), (12), (13), (14), and (15) form part of the wall of vessel(1). As with FIG. 2, (2) is the process fluid and (30) is the heattransfer fluid. The conduits may be formed in a single moulded sheet(44) in which spurs are formed between the conduits to prevent heattransfer between conduits. The reactor is also provided with an externalinsulation jacket (45). The temperature change of the heat transferfluid across the reaction may be measured by the techniques previouslydescribed and the information used to bring the conduits into and out ofoperation as described for the reaction system of FIGS. 2 to 6.

[0160] The invention is useful in slow exothermic reactions includingreactions where large liquid volumes are held. In these reactors thedata is obtained, analysed and used in a manner similar to thecontinuous reactor described above. The benefits of using this equipmentfor slow reactions is that the addition rate of the components can beregulated to prevent accumulation of unreacted chemicals. It is alsopossible to identify the end point of the reaction which offerssubstantial savings in plant utilisation as the product can betransferred forward with the confidence that it satisfies a key qualitycontrol objective. In some cases, accurate identification of end pointalso enhances product quality and yield. The invention also enablesenergy efficiencies and better reaction yields with less waste ofreactants.

[0161] The rate at which heat can be transferred between the processfluid and the heat transfer fluid is dictated (in part) by the overallheat transfer coefficient (U). The larger the value of U, the smallerthe heat transfer area required. The U value may be calculated fromthree components.

[0162] The heat transfer resistance through the process fluid boundarylayer

[0163] The heat transfer resistance through the conduit, preferablycoil, wall

[0164] The heat transfer resistance through the heat transfer fluidboundary layer

[0165] The boundary layers are the stagnant layers of liquid either sideof the conduit, preferably coil, wall. The faster the agitation (orliquid flow), the thinner the boundary layer. Thus high flow rates givebetter heat transfer. Also liquids with good thermal conductivity givebetter heat transfer through the boundary layers.

[0166] Heat transfer mechanism across the conduit, preferably coil, wallis similar, except (unlike the boundary layers) the distance throughwhich the heat has to conduct is fixed.

[0167] Higher heat transfer rates are achieved where the coil materialhas high thermal conductivity. Higher heat transfer rates are alsoachieved where the coil material is thin.

[0168] Thus a high U value requires both a thin conduit, preferablycoil, material (with high thermal conductivity) and turbulent conditionsin both liquids (the more turbulent, the better). The higher the Uvalue, the smaller the area required for heat transfer. This means ashorter heat transfer coil.

[0169] It is therefore preferred to use the thinnest walled conduits,preferably coils, possible without compromising mechanical strength andcorrosion tolerance. A typical wall thickness would be ½ to 4 mm.

[0170] The material from which the conduit, preferably coil, isfabricated is not critical but should be inert to the process fluid.Preferred materials include, stainless steel for non-corrosive organicfluids, Hastelloy C (22 or 276) or similar alloys for most reactionsusing chlorinated solvents or other corrosive compounds. Tantalum andtitanium are suitable where special corrosive conditions exist. In someapplications other materials such as plastic, glass, glass lined steelor ceramics could be used.

[0171] The techniques of the present invention can also be used formeasuring heat of physical changes such as the heat of crystallisationand evaporation.

[0172] The present invention may employ the temperature control meansdescribed in our United Kingdom Patent Application 0121375.0 whichemploys a bank of conduits which are opened and closed to the fluidaccording to a temperature measuring device in the media whosetemperature is to be controlled. The flow of the heat transfer fluid tothe conduits may also be controlled by a multi-port flow control valvesuch as that described in our United Kingdom Patent Application0121071.5.

[0173] In addition the reaction system of the present invention may becalibrated using the techniques described in United Kingdom PatentApplication 0110293.8. Control systems which may be used in the reactionsystem of the present invention are described in United Kingdom PatentApplication 0110295.3. A further modification of the present inventionis described in United Kingdom Patent Application 0110299.5.

[0174] For purposes of illustration only the following examples show thesizing of heat transfer coils.

[0175] Example 1 illustrates the sizing of an individual heat transfercoil such as that used in FIG. 1. Examples 2 and 3 illustrate the sizingand use of multiple heat transfer coil systems.

[0176] In these examples some of the numbers used are arbitrary and arechosen for purposes of illustration only. The examples illustrate thesizing of coils for a batch reactor where an exothermic reaction takesplace. In this, a theoretical reaction reagent A is reacted with productB to produce a new compound C as follows.

A+B C

[0177] where A=kg of A

[0178] B=kg of B

[0179] C=kg of C

[0180] The heat-liberated Hr is as follows:

Hrc=1,000(kJ/kgc) (1)

[0181] The batch reactor is prefilled with component B. Component A isadded slowly (alternatively the two components could be pumpedcontinuously through the reactor in the desired ratios). For thepurposes of this example it is assumed that it is a fast reaction andcomponent B reacts immediately on contact with A. The heat liberated istherefore proportional to the rate of addition (of A). If it is assumedthat the addition rate is such that 0.001 kg/second of C is produced.

[0182] The heat load of the reactor (q)=0.001×1000=1 kW.

[0183] The reaction is also assumed to take place at constanttemperature so that the heat load on the cooling fluid is also 1 kW.

[0184]FIG. 8 is a schematic illustration of a section through a typicalheating/cooling coil such as coil (3) of FIG. 1 in the process fluid (2)through which flows the heat transfer fluid (30).

EXAMPLE 1

[0185] The heat transfer coil (3) serves two functions, it controls theprocess temperature and also measures the quantity of heat liberated (orabsorbed); for the purpose of this example, the term t_(si) is used forthe measured inlet temperature of the heat transfer fluid and t_(so) forthe outlet temperature of the heat transfer fluid. For effectiveoperation, two factors need to be satisfied.

[0186] i The temperature change in the heat transfer fluid(t_(si)−t_(so)) must be sufficiently large to provide a good measurabledifference. For this example a 10° C. temperature change of the heattransfer fluid (t_(si)−t_(so)) has been selected.

[0187] ii In general, the temperature difference between the heattransfer fluid and the process fluid must be as high as possible but notso great that boiling, burning or freezing occur on the pipe surface.Assume that the reaction temperature is 30° C. (t_(p)). Also assume thatthe lowest temperature at which service fluid can be delivered to thesystem is 5° C. (to avoid freezing on the outer surface). Thus theservice fluid inlet temperature (t_(si)) is 5° C. and the outlettemperature (t_(so)) is 15° C. [since (t_(si)−t_(so)) is 10° C.].

[0188] Once the choice for (t_(si)−t_(so)) is made, the mass of the heattransfer fluid can be determined as follows:

m=q/Cp(t _(si) −t _(so))  (1)

[0189] where m=mass flow of heat transfer fluid (kg/s)

[0190] q=heat gain by the heat transfer fluid=1 (kW) (in this example 1kW is the heat of reaction)

[0191] Cp=specific heat of heat transfer fluid=1.6 kJ.kg⁻¹.K⁻¹ (based onthe choice of the synthetic heat transfer fluid)

[0192] t_(si)−t_(so)=temperature change of heat transfer fluid (selectedto be 10° C.)

[0193] Thus from equation (1), the mass flow (m)=1/1.6×10=0.0625 kg/sAssume the density of the heat transfer fluid=840 kg/m³.

[0194] Thus the volume flowrate of the fluid (W)=0.0625/840=0.000074m³/s

[0195] Optimising coil geometry and the velocity of the heat transferfluid is an iterative process. Low velocity of the heat transfer fluidthrough the heat exchange coil gives rise to poor control andmeasurement response. Low velocity also results in a large ratio ofthermal mass of heat transfer fluid to heat load. This tends to magnifyany errors of temperature measurement. High liquid velocity is desirableas it gives faster control response and a better ratio of thermal massto heat load. As the velocity is increased however, the pressure dropthrough the coil gets higher.

[0196] Accordingly the optimum coil will be long enough to give adequateheat transfer area without incurring an excessive pressure drop. If thediameter is too small, the pressure drop will be too high (due to highliquid velocity and long pipe length). If the diameter is too large, theliquid velocity will be too low.

[0197] In this example an initial calculation based on a 4 mm diameterpipe is made for the first iteration as follows:

[0198] At a flowrate of 0.000074 m³/s through a 4 mm bore pipe, thepressure drop of the heat transfer fluid is calculated as being 1.24bar/m (based on synthetic heat transfer fluid).

[0199] The pipe length is calculated from the relationship

L=A/πD(m)

[0200] where L=pipe length=(m)

[0201] A=surface area of pipe (m²)

[0202] D=pipe diameter=0.004 (m)

[0203] π=3.1416

[0204] If the heat exchanger is a plate the parameter equivalent to pipelength is the flow path of the heat transfer fluid though the place andappropriate modifications to the calculation will be required.

[0205] The surface area (A) required for control of the reaction isdetermined from the heat transfer capabilities of the pipe as follows:

A=q/U.LMTD(m ²)

[0206] where A=surface area of pipe (m²)

[0207] U=overall heat transfer coefficient=0.730 (kW.m⁻².K⁻¹) (estimatefor organic process fluid and synthetic oil heat transfer fluid)

[0208]LMTD=[(T_(p)−t_(si))−(T_(p)−t_(so))]/ln[(T_(p)−t_(si))/(T_(p)−t_(so))](° C.) (log mean thermal difference between process and service fluids)

[0209] Also T_(p)=30

[0210] T_(si)=5

[0211] T_(so)=15

[0212] Thus LMTD=19.6 (° C.)

[0213] Therefore A=1/(0.730×19.6)=0.07 m² (m²)

[0214] Therefore L=0.07/(3.1416×0.004)=5.6 (m)

[0215] The pressure drop through the line=5.6×1.24=6.9 bar

[0216] The linear velocity can also be calculated using the continuityequation as follows:

V=W/A

[0217] where V=linear velocity (m/s)

[0218] W=volume flowrate (m³/s)

[0219] A=cross sectional area of the pipe (m²)

[0220] Thus V=0.000074/(π×0.0042/4)=5.9 (m/s)

[0221] A summary of the results of this calculation is shown in table 1below. TABLE 1 Coil duty    1 kW Pipe diameter    4 mm Liquid flowrate0.074 l/s Liquid velocity  5.9 m/s Pipe length  5.6 m Pressure drop  6.9bar

[0222] The table shows that although the 4 mm diameter coil is capableof operating in a reaction that generates 1 kW of heat, it does so atthe expense of very high pressure drop (of the heat transfer fluid). Asmall increase in process load beyond 1 kW would require even higherflowrates and a longer coil which would result in an unacceptably highpressure drop. Thus under the conditions which have been chosen purelyfor the purposes of illustration, at a load of 1 kW the 4 mm diametercoil is at the top end of its operating range.

[0223] A larger pipe diameter of 5 mm internal bore is thereforeselected for the second iteration.

[0224] At a flowrate of 0.000074 m³/s through a 5 mm bore pipe, thepressure drop of the heat transfer fluid is 0.42 bar/m (based on astandard pressure drop calculation synthetic heat transfer fluid).

[0225] The pipe length is again calculated from the relationship

L=A/πD

[0226] where L=pipe length=(m)

[0227] A=surface area of pipe (m²)

[0228] D=pipe diameter=0.005 (m)

[0229] Tr=3.1416

[0230] The required area (A) is determined from the heat transfercapabilities of the pipe using the same formula

A=q/U.LMTD(m ²)

[0231] as was used in the first iteration.

[0232] With the 5 mm coil however, (note the value of U is lower in thiscase (0.66 kW.m⁻².K⁻¹) this is due to the reduced service fluid velocity(which gives a higher service side boundary layer resistance).

[0233] A=1/(0.66×19.6)=0.077 m²

[0234] L=0.077/(3.1416×0.005)=4.9 m

[0235] The pressure drop through the line=4.9×0.42=2.1 bar.

[0236] Also the new velocity is calculated as follows: ThusV=0.000074/(π×0.0052/4)=3.8 (m/s)

[0237] The result of this second calculation is shown in table 2. TABLE2 Coil duty    1 kW Pipe diameter    5 mm Liquid flowrate 0.074 l/sLiquid velocity  3.8 m/s Pipe length  4.9 m Pressure drop  2.1 bar

[0238] The 5 mm diameter coil therefore offers good linear velocitiesand a moderate pressure drop. Such a coil would therefore be useful forthe operating conditions for the reaction used for the purposes of thisexample. The velocity is also well above the minimum preferred value (1m/s).

[0239] To be of practical service, a heat transfer coil needs to operateover a range of conditions as opposed to being limited to one specificheat transfer rate. Table 3 shows the performance of the 5 mm diametercoil under a variety of conditions (for organic process fluid andsynthetic heat transfer oil). The one constant in the table is that thetemperature change of the heat transfer fluid flowing through the coil(t_(si)−t_(so)) is always 10° C. TABLE 3 CALCULATED COIL LENGTHS FOR A 5mm ø COIL Pressure Heat LMTD LMTD LMTD LMTD LMTD Drop capacity Velocity5° C. 10° C. 15° C. 20° C. 25° C. (bar/m) (W) Flow (l/s) m/s (m) (m) (m)(m) (m) 0.1 457 0.033 1.7 8.9 4.4 2.9 2.2 1.8 0.25 761 0.055 2.8 12.46.2 4.2 3.0 2.5 0.50 1121 0.081 4.1 17.2 8.6 5.7 4.3 3.5 0.75 1439 0.1045.3 20.8 10.4 6.9 5.2 4.2 1.00 1660 0.120 6.1 23.6 11.8 7.9 5.9 4.8

[0240] The first column in table 3 shows pressure drop (per metre ofcoil) through the coil for a given flow rate. The second column givesthe heating or cooling capacity of the coil based on the 10° C.temperature change. The third and fourth columns give the volume flowrate and velocity of the liquid. The last five columns give minimum coillengths required for the quoted LMTD values. The LMTD temperature valuesquoted at the top of these columns represent the log mean temperaturedifference between the heat transfer fluid and the process fluid.

[0241] It can be seen from table 3 that different coil lengths are useddepending on process heat load and log mean temperature differencebetween the process and service fluids. Table 3 shows that a largetemperature difference is beneficial, as it requires shorter coillengths.

[0242] From table 3, a good general-purpose coil would be 5.9 metres inlength. This would be capable of serving any of the duties contemplatedin table 3 where the required coil length was 5.9 metres or less. Itwould be suitable for a process load of 1.66 kW providing the differencein temperature between process and heat transfer fluid was at least 20°C. Under these conditions the pressure drop through the coil would be5.9 bar.

[0243] The coil also offers adequate heat transfer area and reasonablecontrol response at heat loads down to 0.46 kW. Although low velocitiesare tolerable the control system becomes increasingly sluggish with lowflows. Also low velocities result in a large ratio of thermal mass (ofheat transfer fluid) to heat load. This tends to magnify any errors oftemperature measurement. High liquid velocity is therefore desirable asit gives faster control response and a better (lower) ratio of thermalmass (of the heat transfer fluid) to heat load.

[0244] For the reasons given above, high heat transfer fluid velocitiesare generally desirable.

[0245] Very high pressure drops however also introduce greater energyfrom turbulence and friction. There are also practical equipmentconstraints on how fast a liquid can be pumped through a pipe. Thesingle coil system of example 1 is useful, but has its limitations.

[0246] As example 1 illustrates, a single coil has an optimum operatingrange. Although it is capable of measuring a range of heat transferrates, it has its limitations. As table 3 shows, at heat transfer ratesabove 1121 W, the pressure drop across the coil increases rapidly due tothe need for increasingly longer pipes and higher pressure drops permeter of pipe length.

[0247] The limitations of the single coil may be illustrated as follows:

[0248] A coil 6.2 m long operating with an LMTD (log mean temperaturedifference between the process fluid and service fluid) of 10° C. has anominal operating range of 457-1121 W. At maximum load, the pressuredrop across the coil would be 1.55 bar. If this coil was to be used witha heat load of 1660 W under the same conditions, it would have to be11.8 meters long and the corresponding pressure drop would be 11.8 bar.If, under the same conditions, the LMTD was reduced to 5° C., the pipewould need to be 23.6 meters long and the resulting pressure drop wouldbe 23.6 bar.

[0249] Although the range of a coil can be increased by varying theinlet temperature (t_(si)), there are limitations. If the temperaturedifference (t_(si)−t_(so)) is reduced, the system becomes progressivelyless accurate due to limitations of the temperature measuring devices.If the temperature difference (t_(si)−t_(so)) is expanded too far, thereis a risk of freezing the process fluid (or surface boiling or heatdamage where heat is being absorbed by the process fluid).

[0250] Although service fluid flow and supply temperatures are bothparameters that can be varied to alter the operating range, reliablecontrol methods favour using one control parameter at a time (and stepchanging the other where necessary).

[0251] The 5 mm diameter coil illustrated in example 1 gives a turn downratio of approximately 2.5 (1121/457). If the temperature differenceacross the coil (t_(si)−t_(so)) was increased from 10° C. to 20° C., theturn down ratio could be increased to 5. An alternative method ofincreasing the operating range of the system is to use multiple coils ina cascade fashion, which provide a variable area heat transfer surface.Such a system is illustrated by the following

EXAMPLE 2

[0252] Example 2 illustrates, the design of variable area heat transfersystems employing multiple coil systems such as those illustrated inFIGS. 2 and 3. As in example 1, the cooling (or heating) coil systemcontrols the process temperature and continuously measures the heatgained or lost using information on mass flowrate through the coil,temperature change (t_(si)−t_(so)) and specific heat of the heattransfer fluid.

[0253] Example 2 addresses the fact that a reactor might be required tohandle exothermic reactions, which generate heat in the range of 500 to15,000 W. A range of this size exceeds the operating capabilities of thesingle heat transfer coil system illustrated in example 1. Such areactor can however be effectively operated using multiple coils asillustrated in this example (in this example identical coils each 11.8 mlong are used) in a cascade fashion. With one coil operating with theheat transfer fluid at 1.7 m/s, a heat load of 457 W will give atemperature rise in service fluid (t_(si)−t_(so)) of 10° C. If, underthe same conditions the velocity of the heat transfer fluid is increasedto 6.1 m/second the capacity rises to 1,660 W (see table 3). If twocoils are used at maximum flow the capacity is 3,320 W. By adding coilsin this manner ever-greater heat loads can be measured. If, for example,ten coils are used at the maximum flow, the capacity is 16,600 W. Thissystem therefore offers a turndown ratio of approximately 36(16,600/457). Accordingly, by varying the velocity of the fluid and thenumber of coils, the heat capacity can be measured with a high degree ofaccuracy over a wide range.

[0254] The devices described so far have turndown capacities of up to36. In practice, a turndown of 1000 or more may be desirable. This couldbe important with a batch reaction where the end point needs to beidentified with precision. Alternatively, high turndown would be usefulfor process operations that switch from batch to continuous operation.In other cases, the same piece of equipment might be used on multipleapplications of widely varying energy release (or absorption) rates. Theindividual coil turn down capabilities described above (temperature,flow rate) enable the system to be adapted for different operatingconditions. It must be recognised however that in normal operationconstant flow and temperature to each conduit is desirable. For thisreason a large number of conduits deliver the best representation ofvariable area control (with all the benefits that brings). Whilst thedevice previously described has considerable use it has its limitationfor this type of application, because an impractical number of coilswould be needed. Therefore an alternative embodiment of the inventionuses a plurality of coils for varying available heat transfer area asillustrated in example 3.

EXAMPLE 3

[0255] Table 4 sets out the heat transfer capacities of a series ofcoils of varying diameter and length. TABLE 4 Coil Coil length Operatingdiameter range range (mm) (m) (W) 1 0.13-0.6  4-22 2  0.9-2.3  40-141 3 1.9-4.7 118-429 4  3.0-7.8 249-913 5  4.4-11.8 457-1660

[0256] In order to arrive at the operating range, as with examples 1 and2, the LMTD is taken as 10° C. and (t_(si)−t_(so)) as 10° C. Theextremes of the ranges set out in columns two and three of table 4represent the calculated values for minimum and maximum flow of the heattransfer fluid. Minimum flow is that which results in a pressure drop(of service fluid) of 0.1 bar.m⁻¹ and maximum flow that which results ina pressure drop (of service fluid) of 1 bar.m⁻¹.

[0257] This combination of coil diameters and lengths provides a systemcapable of very high turndown rations. For example a six-coil reactorcan be designed to operate at less than 4 W and up to 5000 W. Table 5shows the cumulative capacity of 6 coils of varying diameter. TABLE 5Cumulative Coil Coil diameter Coil range range number (mm) (W) (W) 1 1mm  4-22 4-22 2 1 mm  4-22 4-44 3 2 mm  40-141 4-185 4 3 mm 118-4294-614 5 5 mm 457-1660 4-2274 6 5 mm 457-1660 4-3934

[0258] Each coil is sized for the maximum length shown in table 4. Thenominal turndown ratio of the six coils is 984.

[0259] If (t_(si)−t_(so)) is stepped down to 5° C. when a single 1 mmdiameter coil is operating, the nominal turndown ratio is increased to1967 (2-3934 W).

[0260] If (t_(si)−t_(so)) is stepped up to 20° C. when all the coils areoperating the nominal turndown ratio is increased to 3934 (2-7868 W).

[0261] The six-coil arrangement described above offers a good operatingrange. To achieve smooth heat flow transition as coils open up howeveris more difficult to achieve. There are two options on a six-coiledsystem. Firstly the supply pressure or temperature can be varied toprovide intermediate heating/cooling capacities. Alternatively theon/off valves can be operated in a more complex sequence. The preferredsolution however is to use more coils. For example a system might use 10of 1 mm φ coils 10 of 2 mm diameter coils and 10 of 3 mm φ coils.

[0262] The invention therefore enables a very large operating range withsimple reactor design.

[0263] In some cases, rigorous analysis may require greater overlap (interms of operating range) to ensure that pipes when opened can operatein the preferred fluid velocity range.

[0264] The invention can be used to improve the operation of commercialchemical and physical reaction systems. It can however also be used toprovide considerably smaller reaction systems with comparable commercialthroughput. For example the invention enables reduction of reactor sizeby a factor of 10 and, in some instances, a factor of 100 or greater. Inparticular it can be applied to current commercial

[0265] batch organic synthesis reactions currently carried out inreactors of 10 to 20,000 litres.

[0266] bulk pharmaceutical synthesis reactions currently carried out inreactions of 10 to 20,000 litres.

[0267] batch polymerisation reactions currently carried out in reactorsof 10 to 20,000 litres.

[0268] batch synthesis reactions of 10 to 20,000 litres currently usedfor unstable materials (compounds susceptible to self-acceleratingrunaways)

[0269] batch inorganic synthesis reactions currently carried out inreactions of 10 to 20,000 litres.

[0270] The techniques may also be useful in larger scale chemical andpetrochemical operations.

[0271] This technology will also be of value as a research anddevelopment tool where it gives the user the combination of accuratecalorimetry and good temperature control. In this capacity it would beused in equipment of 1 ml to 10 litres capacity. This technology canalso be used for small-scale reaction applications. In this capacity itwould be used for reaction equipment of 1 ml to 10 ml capacity.

1. A reaction system comprising a reactor containing a reaction processmedium and a heat exchanger providing a conduit through which flows aheat transfer fluid wherein measurement of the flow and temperaturechange of the heat transfer fluid across the reaction is used todetermine the heat generated or absorbed by the reaction system and thatdetermination is used to monitor and control the reaction wherein i. theaverage temperature difference between the heat transfer fluid and theprocesses fluid is from 1 to 1000° C. ii. the temperature differential(t_(si)−t_(so)) of the heat transfer fluid across the reaction system isat least 0.1° C. iii. the linear velocity of the heat transfer fluid isat least 0.01 meters/second.
 2. A reaction system according to claim 1,in which the average temperature difference between the heat fluid andthe process fluid is from 1 to 100° C.
 3. A reaction system according toclaim 1, in which the temperature differential (t_(si)−t_(so)) of theheat transfer fluid across the reaction system is at least 1° C.
 4. Areaction system according to claim 1, in which the linear velocity ofthe heat transfer fluid is at least 0.1 meters/second.
 5. A reactionsystem according to claim 1, in which the heat exchanger has sufficientsurface area to ensure that a measurable temperature difference(t_(si)−t_(so)) is observed in the heat transfer fluid as it passesacross the reactor.
 6. A reaction system according to claim 1, in which(t_(si)−t_(so)) is 10° C. or more.
 7. A reaction system according toclaim 1, in which a temperature difference of above 5° C. is maintainedbetween the process fluid and the inlet heat transfer fluid (t_(si)). 8.A reaction system according to claim 7, in which the temperaturedifference is from 5° C. to 100° C.
 9. A reaction system according toclaim 1, in which the heat transfer fluid flows at a velocity of atleast 1 meter/second.
 10. A reaction system according to claim 1, inwhich the heat transfer fluid is supplied at substantially constanttemperature and pressure.
 11. A reaction system according to claim 1, inwhich the heat exchanger for the reactor is a heat transfer coil, whichpasses through the reaction process medium.
 12. A reaction systemaccording to claims 1, in which the heat exchanger is a plate which issubmerged in the reaction process medium.
 13. A reaction systemaccording to claim 1, in which the heat exchanger is or forms part ofthe vessel wall.
 14. A reaction system according to claim 1, in whichthe heat transfer fluid is recycled.
 15. A reaction system according toclaim 11, in which the diameter to length relationship of a heattransfer coil is calculated by first calculating the heat transfer arearequired using the formula U.A.LMTD=m.Cp.(t _(si) −t _(so))(kW) whereU=overall heat transfer coefficient (kW.m⁻².K⁻¹) A=heat transfer area(m²) m=mass flow rate of heat transfer fluid (kg/s) LMTD=log meanthermal difference between service and process fluids (° C.) Cp=specificheat of heat transfer fluid (kJ.kg⁻¹K⁻¹) (t_(si)−t_(so))=temperature (°C.) change in the heat transfer fluid between inlet and outlet and thediameter to length relationship of the coil is developed to enable highReynolds number in the heat transfer fluid without an excessive pressuredrop.
 16. A reaction system according to claims 12, in which the heattransfer area is calculated from the formula U.A.LMTD=m.Cp.(t _(si) −t_(so))(kW) where U=overall heat transfer coefficient (kW.m⁻².K⁻¹) A=heattransfer area (m²) m=mass flow rate of heat transfer fluid (kg/s)LMTD=log mean thermal difference between service and process fluids (°C.) Cp=specific heat of heat transfer fluid (kJ.kg⁻¹K⁻¹)(t_(si)−t_(so))=temperature (° C.) change in the heat transfer fluidbetween inlet and outlet and the area to fluid path relationship isdeveloped to enable high Reynolds number in the heat transfer fluidwithout an excessive pressure drop.
 17. A reaction system according toclaim 1, in which the pressure drop across the conduits is 0.001 to 20bar.
 18. A reaction system according to claim 17, in which the pressuredrop across the conduits is 0.1 to 20 bar.
 19. A reaction systemaccording to preceding claim 1, in which the heat exchanger is such thatthe area available for heat transfer between the reaction process mediumand the heat transfer fluid may be varied according to the needs of theparticular reaction.
 20. A reaction system according to claim 19, inwhich the area of heat transfer is varied by providing multiple heattransfer pipes each of which has a diameter and length relationshipdesigned to provide a certain degree of heat transfer.
 21. A reactionsystem according to claim 19, in which the area of heat transfer isvaried by providing multiple heat transfer plates each of which has asurface area and hydraulic path relationship designed to provide acertain degree of heat transfer.
 22. A reaction system according toclaim 19, in which the heat exchanger is or forms part of the reactionvessel wall and consists of multiple conduits each designed to provide acertain degree of heat transfer.
 23. A method for synthesis reactionswhich comprises: flowing a heat transfer fluid through a conduitdisposed in a reactor comprising a reaction process medium and a heatexchanger; and determining the flow and temperature change of the heattransfer fluid across the reaction, thereby determining the heatgenerated or absorbed by the reaction system and using thatdetermination to monitor and control the reaction wherein i. the averagetemperature difference between the heat transfer fluid and the processesfluid is from 1 to 1000° C. ii. the temperature differential(t_(si)−t_(so)) of the heat transfer fluid across the reaction system isat least 0.1° C. iii. the linear velocity of the heat transfer fluid isat least 0.01 meters/second.
 24. The method according to claim 23 forfast exothermic reactions.
 25. The method according to claim 23, whereinsaid reaction is a batch organic synthesis reactions carried out inreactions of 10 to 20,000 litres.
 26. The method according to claim 23,wherein said reaction is a bulk pharmaceutical synthesis reactioncarried out in reactions of 10 to 20,000 litres.
 27. The methodaccording to claim 23, wherein said reaction is a batch polymerisationreaction carried out in reactions of 10 to 20,000 litres.
 28. The methodaccording to claim 23, wherein said reaction is a batch synthesisreactions of 10 to 20,000 litres used for unstable materials.
 29. Themethod according to claim 23, wherein said reaction is a batch inorganicsynthesis reaction carried out in reactions of 10 to 20,000 litres. 30.The method according to claim 23, wherein said reaction is a continuousreaction.
 31. The method according to claim 23, wherein said reaction iscarried out in a reactor of from 1 ml to 10 litres capacity.